Control of Glutamate Transport by Extracellular Potassium: Basis for a Negative Feedback on Synaptic Transmission.

Glutamate and K+, both released during neuronal firing, need to be tightly regulated to ensure accurate synaptic transmission. Extracellular glutamate and K+ ([K+]o) are rapidly taken up by glutamate transporters and K+-transporters or channels, respectively. Glutamate transport includes the exchange of one glutamate, 3 Na+, and one proton, in exchange for one K+. This K+ efflux allows the glutamate binding site to reorient in the outwardly facing position and start a new transport cycle. Here, we demonstrate the sensitivity of the transport process to [K+]o changes. Increasing [K+]o over the physiological range had an immediate and reversible inhibitory action on glutamate transporters. This K+-dependent transporter inhibition was revealed using microspectrofluorimetry in primary astrocytes, and whole-cell patch-clamp in acute brain slices and HEK293 cells expressing glutamate transporters. Previous studies demonstrated that pharmacological inhibition of glutamate transporters decreases neuronal transmission via extrasynaptic glutamate spillover and subsequent activation of metabotropic glutamate receptors (mGluRs). Here, we demonstrate that increasing [K+]o also causes a decrease in neuronal mEPSC frequency, which is prevented by group II mGluR inhibition. These findings highlight a novel, previously unreported physiological negative feedback mechanism in which [K+]o elevations inhibit glutamate transporters, unveiling a new mechanism for activity-dependent modulation of synaptic activity

DO Leonis - a new eclipsing cataclysmic variable

Photometric and spectroscopic observations of DO Leo have been obtained using the McDonald Observatory high-speed CCD photometer and a conventional two-channel photoelectric photometer. The data reveal eclipses that are approximately 1.5 m deep. A total of nine eclipses were observed in February and March 1988 and in April 1989. These data were used to establish an orbital period of 0.2345147(2) d. A low-resolution optical spectrum reveals significant He II 4686 emission in addition to the characteristic Balmer and He I emission lines

Using an Ellipsoid Model to Track and Predict the Evolution and Propagation of Coronal Mass Ejections

We present a method for tracking and predicting the propagation and evolution of coronal mass ejections (CMEs) using the imagers on the STEREO and SOHO satellites. By empirically modeling the material between the inner core and leading edge of a CME as an expanding, outward propagating ellipsoid, we track its evolution in three-dimensional space. Though more complex empirical CME models have been developed, we examine the accuracy of this relatively simple geometric model, which incorporates relatively few physical assumptions, including i) a constant propagation angle and ii) an azimuthally symmetric structure. Testing our ellipsoid model developed herein on three separate CMEs, we find that it is an effective tool for predicting the arrival of density enhancements and the duration of each event near 1 AU. For each CME studied, the trends in the trajectory, as well as the radial and transverse expansion are studied from 0 to ~.3 AU to create predictions at 1 AU with an average accuracy of 2.9 hours.Comment: 18 pages, 11 figure

Downscaling Changing Coastlines in a Changing Climate: The Hybrid Approach

Shifts in the frequency of typical meteorological patterns in an ocean basin, over interannual to decadal time scales, cause shifts in the patterns of wave generation. Therefore, ocean basin-scale climate shifts produce shifts in the wave climates affecting the coastlines of the basin. We present a hybrid methodology for downscaling observed (or predicted) climate shifts into local nearshore wave climates and then into the associated coastline responses. A series of statistical analyses translate observed (or predicted) distributions of meteorological states into the deep water wave climate affecting a coastal region and dynamical modeling combined with statistical analyses transform the deep water wave climate into the nearshore wave climate affecting a particular coastline. Finally, dynamical modeling of coastline evolution hindcasts (or predicts) how coastline shapes respond to climate shifts. As a case study, we downscale from meteorological hindcast in the North Atlantic basin since 1870 to the responses of the shape of the coast of the Carolinas, USA. We test the hindcasts using shoreline change rates calculated from historical shorelines, because shifts in coastline shape equate to changes in the alongshore pattern of shoreline change rates from one historical period to another. Although limited by the availability of historical shorelines (and complicated by historical inlet openings), the observations are consistent with the predicted signal of ocean basin-scale climate change. The hybrid downscaling methodology, applied to the output of global climate models, can be used to help forecast future patterns of shoreline change related to future climate change scenarios

Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue.

Lactate can be used by neurons as an energy substrate to support their activity. Evidence suggests that lactate also acts on a metabotropic receptor called HCAR1, first described in the adipose tissue. Whether HCAR1 also modulates neuronal circuits remains unclear. In this study, using qRT-PCR, we show that HCAR1 is present in the human brain of epileptic patients who underwent resective surgery. In brain slices from these patients, pharmacological HCAR1 activation using a non-metabolized agonist decreased the frequency of both spontaneous neuronal Ca <sup>2+</sup> spiking and excitatory post-synaptic currents (sEPSCs). In mouse brains, we found HCAR1 expression in different regions using a fluorescent reporter mouse line and in situ hybridization. In the dentate gyrus, HCAR1 is mainly present in mossy cells, key players in the hippocampal excitatory circuitry and known to be involved in temporal lobe epilepsy. By using whole-cell patch clamp recordings in mouse and rat slices, we found that HCAR1 activation causes a decrease in excitability, sEPSCs, and miniature EPSCs frequency of granule cells, the main output of mossy cells. Overall, we propose that lactate can be considered a neuromodulator decreasing synaptic activity in human and rodent brains, which makes HCAR1 an attractive target for the treatment of epilepsy

Statewide geographic variation in outcomes for adults with acute myeloid leukemia in North Carolina

BACKGROUND: Population-based studies have demonstrated survival disparities related to socioeconomic factors for patients with acute myeloid leukemia (AML). The objective of the current study was to determine whether the local health care infrastructure, represented by Area Health Education Centers (AHEC) region, or treating center experience, represented by National Cancer Institute Comprehensive Cancer Center (NCICCC) designation, were associated with outcomes among patients with AML in North Carolina. METHODS: Patients who were diagnosed with AML from 2003 to 2009 were identified using the University of North Carolina Lineberger Integrated Cancer Information and Surveillance System, a database linking insurance claims to the North Carolina Cancer Registry. A Cox proportional-hazards model was used to explore survival based on AHEC region. A subset of patients who received inpatient chemotherapy was examined to evaluate the impact of treatment at an NCICCC. RESULTS: Nine hundred patients were identified in the study period, 553 of whom received inpatient chemotherapy therapy within 30 days of diagnosis. Almost one-half of these patients (n5294) received chemotherapy at a non-NCICCC. Among the patients who received intensive inpatient therapy, residence in 3 of 9 AHEC regions was associated with a higher risk of mortality (hazard ratio: range, 1.97-4.03; P<.01) at 1 year in multivariate analysis. Treatment at a non-NCICCC was not associated with an increased risk of mortality at 1 year (hazard ratio, 1.25; 95% confidence interval, 0.95-1.65). CONCLUSIONS: Survival among patients with AML in North Carolina varies according to geographic region. Further examination of local practice and referral patterns may inform strategies to improve AML outcomes across the state